Skip to main content
Log in

Interchromosomal effect in carriers of translocations and inversions assessed by preimplantation genetic testing for structural rearrangements (PGT-SR)

  • Genetics
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

Balanced carriers of structural rearrangements have an increased risk of unbalanced embryos mainly due to the production of unbalanced gametes during meiosis. Aneuploidy for other chromosomes not involved in the rearrangements has also been described. The purpose of this work is to know if the incidence of unbalanced embryos, interchromosomal effect (ICE) and clinical outcomes differ in carriers of different structural rearrangements.

Methods

Cohort retrospective study including 359 preimplantation genetic testing cycles for structural rearrangements from 304 couples was performed. Comparative genomic hybridisation arrays were used for chromosomal analysis. The results were stratified and compared according to female age and carrier sex. The impact of different cytogenetic features of chromosomal rearrangements was evaluated.

Results

In carriers of translocations, we observed a higher percentage of abnormal embryos from day 3 biopsies compared with day 5/6 biopsies and for reciprocal translocations compared with other rearrangements. We observed a high percentage of embryos with aneuploidies for chromosomes not involved in the rearrangement that could be attributed to total ICE (aneuploid balanced and unbalanced embryos). No significant differences were observed in these percentages between types of rearrangements. Pure ICE (aneuploid balanced embyos) was independent of female age only for Robertsonian translocations, and significantly increased in day 3 biopsies for all types of abnormalities. Furthermore, total ICE for carriers of Robertsonian translocations and biopsy on day 3 was independent of female age too. High ongoing pregnancy rates were observed for all studied groups, with higher pregnancy rate for male carriers.

Conclusion

We observed a higher percentage of abnormal embryos for reciprocal translocations. No significant differences for total ICE was found among the different types of rearrangements, with higher pure ICE only for Robertsonian translocations. There was a sex effect for clinical outcome for carriers of translocations, with higher pregnancy rate for male carriers. The higher incidence of unbalanced and aneuploid embryos should be considered for reproductive counselling in carriers of structural rearrangements.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Jacobs PA, Melville M, Ratcliffe S, Keay AJ, Syme J. A cytogenetic survey of 11,680 newborn infants. Ann Hum Genet. 1974;37:359–76.

    CAS  PubMed  Google Scholar 

  2. Van Dyke DL, Weiss L, Roberson JR, Babu VR. The frequency and mutation rate of balanced autosomal rearrangements in man estimated from prenatal genetic studies for advanced maternal age. Am J Hum Genet. 1983;35:301–8.

    PubMed  PubMed Central  Google Scholar 

  3. Campana M, Serra A, Neri G. Role of chromosome aberrations in recurrent abortion: a study of 269 balanced translocations. Am J Med Genet. 1986;24:341–56.

    CAS  PubMed  Google Scholar 

  4. Fryns JP, Van Buggenhout G. Structural chromosome rearrangements in couples with recurrent fetal wastage. Eur J Obstet Gynecol Reprod Biol. 1998;81:171–6.

    CAS  PubMed  Google Scholar 

  5. Stern C, Pertile M, Norris H, Hale L, Baker HW. Chromosome translocations in couples with in-vitro fertilization implantation failure. Hum Reprod. 1999;14:2097–101.

    CAS  PubMed  Google Scholar 

  6. Neri G, Serra A, Campana M, Tedeschi B. Reproductive risks for translocation carriers: cytogenetic study and analysis of pregnancy outcome in 58 families. Am J Med Genet. 1983;16:535–61.

    CAS  PubMed  Google Scholar 

  7. Scriven PN, Handyside AH, Ogilvie CM. Chromosome translocations: segregation modes and strategies for preimplantation genetic diagnosis. Prenat Diagn. 1998;18:1437–49.

    CAS  PubMed  Google Scholar 

  8. Anton E, Vidal F, Blanco J. Reciprocal translocations: tracing their meiotic behavior. Genet Med. 2008;10:730–8.

    PubMed  Google Scholar 

  9. Conn CM, Harper JC, Winston RM, Delhanty JD. Infertile couples with Robertsonian translocations: preimplantation genetic analysis of embryos reveals chaotic cleavage divisions. Hum Genet. 1998;102:117–23.

    CAS  PubMed  Google Scholar 

  10. Fischer J, Colls P, Escudero T, Munne S. Preimplantation genetic diagnosis (PGD) improves pregnancy outcome for translocation carriers with a history of recurrent losses. Fertil Steril. 2010;94:283–9.

    PubMed  Google Scholar 

  11. Munne S, Sandalinas M, Escudero T, Fung J, Gianaroli L, Cohen J. Outcome of preimplantation genetic diagnosis of translocations. Fertil Steril. 2000;73:1209–18.

    CAS  PubMed  Google Scholar 

  12. Verlinsky Y, Tur-Kaspa I, Cieslak J, Bernal A, Morris R, Taranissi M, et al. Preimplantation testing for chromosomal disorders improves reproductive outcome of poor-prognosis patients. Reprod BioMed Online. 2005;11:219–25.

    CAS  PubMed  Google Scholar 

  13. Munne S, Bahce M, Schimmel T, Sadowy S, Cohen J. Case report: chromatid exchange and predivision of chromatids as other sources of abnormal oocytes detected by preimplantation genetic diagnosis of translocations. Prenat Diagn. 1998;18:1450–8.

    CAS  PubMed  Google Scholar 

  14. Munne S, Morrison L, Fung J, Marquez C, Weier U, Bahce M, et al. Spontaneous abortions are reduced after preconception diagnosis of translocations. J Assist Reprod Genet. 1998;15:290–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Verlinsky Y, Evsikov S. Karyotyping of human oocytes by chromosomal analysis of the second polar bodies. Mol Hum Reprod. 1999;5:89–95.

    CAS  PubMed  Google Scholar 

  16. Harper JC, Wilton L, Traeger-Synodinos J, Goossens V, Moutou C, SenGupta SB, et al. The ESHRE PGD Consortium: 10 years of data collection. Hum Reprod Update. 2012;18:234–47.

    CAS  PubMed  Google Scholar 

  17. DeUgarte CM, Li M, Surrey M, Danzer H, Hill D, DeCherney AH. Accuracy of FISH analysis in predicting chromosomal status in patients undergoing preimplantation genetic diagnosis. Fertil Steril. 2008;90:1049–54.

    CAS  PubMed  Google Scholar 

  18. Munne S. Preimplantation genetic diagnosis of numerical and structural chromosome abnormalities. Reprod BioMed Online. 2002;4:183–96.

    PubMed  Google Scholar 

  19. Velilla E, Escudero T, Munne S. Blastomere fixation techniques and risk of misdiagnosis for preimplantation genetic diagnosis of aneuploidy. Reprod BioMed Online. 2002;4:210–7.

    PubMed  Google Scholar 

  20. Fiorentino F, Kokkali G, Biricik A, Stavrou D, Ismailoglu B, De Palma R, et al. Polymerase chain reaction-based detection of chromosomal imbalances on embryos: the evolution of preimplantation genetic diagnosis for chromosomal translocations. Fertil Steril. 2010;94:2001-11, 2011.e1-6.

    PubMed  Google Scholar 

  21. Lukaszuk K, Pukszta S, Ochman K, Cybulska C, Liss J, Pastuszek E, et al. Healthy baby born to a Robertsonian translocation carrier following next-generation sequencing-based preimplantation genetic diagnosis: a case report. AJP Rep. 2015;5:e172–5.

    PubMed  PubMed Central  Google Scholar 

  22. Tan YQ, Tan K, Zhang SP, Gong F, Cheng DH, Xiong B, et al. Single-nucleotide polymorphism microarray-based preimplantation genetic diagnosis is likely to improve the clinical outcome for translocation carriers. Hum Reprod. 2013;28:2581–92.

    CAS  PubMed  Google Scholar 

  23. Treff NR, Tao X, Schillings WJ, Bergh PA, Scott RT Jr, Levy B. Use of single nucleotide polymorphism microarrays to distinguish between balanced and normal chromosomes in embryos from a translocation carrier. Fertil Steril. 2011;96:e58–65.

    PubMed  Google Scholar 

  24. van Uum CM, Stevens SJ, Dreesen JC, Drusedau M, Smeets HJ, Hollanders-Crombach B, et al. SNP array-based copy number and genotype analyses for preimplantation genetic diagnosis of human unbalanced translocations. Eur J Hum Genet. 2012;20:938–44.

    PubMed  PubMed Central  Google Scholar 

  25. Xie Y, Xu Y, Wang J, Miao B, Zeng Y, Ding C, Gao J, Zhou C. Preliminary analysis of numerical chromosome abnormalities in reciprocal and Robertsonian translocation preimplantation genetic diagnosis cases with 24-chromosomal analysis with an aCGH/SNP microarray. J Assist Reprod Genet. 2018 Jan;35(1):177–186.

    PubMed  PubMed Central  Google Scholar 

  26. Alfarawati S, Fragouli E, Colls P, Wells D. First births after preimplantation genetic diagnosis of structural chromosome abnormalities using comparative genomic hybridization and microarray analysis. Hum Reprod. 2011;26:1560–74.

    CAS  PubMed  Google Scholar 

  27. Fiorentino F, Spizzichino L, Bono S, Biricik A, Kokkali G, Rienzi L, et al. PGD for reciprocal and Robertsonian translocations using array comparative genomic hybridization. Hum Reprod. 2011;26:1925–35.

    CAS  PubMed  Google Scholar 

  28. Li G, Jin H, Xin Z, Su Y, Brezina PR, Benner AT, et al. Increased IVF pregnancy rates after microarray preimplantation genetic diagnosis due to parental translocations. Syst Biol Reprod Med. 2014;60:119–24.

    PubMed  Google Scholar 

  29. Tobler KJ, Brezina PR, Benner AT, Du L, Xu X, Kearns WG. Two different microarray technologies for preimplantation genetic diagnosis and screening, due to reciprocal translocation imbalances, demonstrate equivalent euploidy and clinical pregnancy rates. J Assist Reprod Genet. 2014;31:843–50.

    PubMed  PubMed Central  Google Scholar 

  30. Bono S, Biricik A, Spizzichino L, Nuccitelli A, Minasi MG, Greco E, et al. Validation of a semiconductor next-generation sequencing-based protocol for preimplantation genetic diagnosis of reciprocal translocations. Prenat Diagn. 2015;35:938–44.

    CAS  PubMed  Google Scholar 

  31. Wang L, Cram DS, Shen J, Wang X, Zhang J, Song Z, et al. Validation of copy number variation sequencing for detecting chromosome imbalances in human preimplantation embryos. Biol Reprod. 2014;91:37.

    PubMed  Google Scholar 

  32. Lejeune J. Autosomal disorders. Pediatrics. 1963;32:326–37.

    CAS  PubMed  Google Scholar 

  33. Anton E, Vidal F, Blanco J. Interchromosomal effect analyses by sperm FISH: incidence and distribution among reorganization carriers. Syst Biol Reprod Med. 2011;57:268–78.

    CAS  PubMed  Google Scholar 

  34. Anton E, Blanco J, Egozcue J, Vidal F. Sperm FISH studies in seven male carriers of Robertsonian translocation t(13;14)(q10;q10). Hum Reprod. 2004;19:1345–51.

    CAS  PubMed  Google Scholar 

  35. Blanco J, Egozcue J, Clusellas N, Vidal F. FISH on sperm heads allows the analysis of chromosome segregation and interchromosomal effects in carriers of structural rearrangements: results in a translocation carrier, t(5;8)(q33;q13). Cytogenet Cell Genet. 1998;83:275–80.

    CAS  PubMed  Google Scholar 

  36. Douet-Guilbert N, Bris MJ, Amice V, Marchetti C, Delobel B, Amice J, et al. Interchromosomal effect in sperm of males with translocations: report of 6 cases and review of the literature. Int J Androl. 2005;28:372–9.

    CAS  PubMed  Google Scholar 

  37. Escudero T, Lee M, Carrel D, Blanco J, Munne S. Analysis of chromosome abnormalities in sperm and embryos from two 45,XY,t(13;14)(q10;q10) carriers. Prenat Diagn. 2000;20:599–602.

    CAS  PubMed  Google Scholar 

  38. Godo A, Blanco J, Vidal F, Sandalinas M, Garcia-Guixe E, Anton E. Altered segregation pattern and numerical chromosome abnormalities interrelate in spermatozoa from Robertsonian translocation carriers. Reprod BioMed Online. 2015;31:79–88.

    PubMed  Google Scholar 

  39. Alfarawati S, Fragouli E, Colls P, Wells D. Embryos of robertsonian translocation carriers exhibit a mitotic interchromosomal effect that enhances genetic instability during early development. PLoS Genet. 2012;8:e1003025.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Durban M, Benet J, Boada M, Fernandez E, Calafell JM, Lailla JM, et al. PGD in female carriers of balanced Robertsonian and reciprocal translocations by first polar body analysis. Hum Reprod Update. 2001;7:591–602.

    CAS  PubMed  Google Scholar 

  41. Gutierrez-Mateo C, Gadea L, Benet J, Wells D, Munne S, Navarro J. Aneuploidy 12 in a Robertsonian (13;14) carrier: case report. Hum Reprod. 2005;20:1256–60.

    CAS  PubMed  Google Scholar 

  42. Gianaroli L, Magli MC, Ferraretti AP, Munne S, Balicchia B, Escudero T, et al. Possible interchromosomal effect in embryos generated by gametes from translocation carriers. Hum Reprod. 2002;17:3201–7.

    CAS  PubMed  Google Scholar 

  43. Tulay P, Gultomruk M, Findikli N, Yagmur E, Bahceci M. Is the interchromosomal effect present in embryos derived from Robertsonian and reciprocal translocation carriers particularly focusing on chromosome 10 rearrangements? Zygote. 2015;23:908–15.

    CAS  PubMed  Google Scholar 

  44. Rubio C, Mercader A, Alama P, Lizan C, Rodrigo L, Labarta E, et al. Prospective cohort study in high responder oocyte donors using two hormonal stimulation protocols: impact on embryo aneuploidy and development. Hum Reprod. 2010;25:2290–7.

    CAS  PubMed  Google Scholar 

  45. Cobo A, Bellver J, Domingo J, Perez S, Crespo J, Pellicer A, et al. New options in assisted reproduction technology: the Cryotop method of oocyte vitrification. Reprod BioMed Online. 2008;17:68–72.

    PubMed  Google Scholar 

  46. Beyer CE, Willats E. Natural selection between day 3 and day 5/6 PGD embryos in couples with reciprocal or Robertsonian translocations. J Assist Reprod Genet. 2017 Nov;34(11):1483–1492.

    PubMed  PubMed Central  Google Scholar 

  47. Amir H, Barbash-Hazan S, Kalma Y, Frumkin T, Malcov M, Samara N, et al. Time-lapse imaging reveals delayed development of embryos carrying unbalanced chromosomal translocations. J Assist Reprod Genet. 2019;36:315–24.

    PubMed  Google Scholar 

  48. Rodrigo L, Mateu E, Mercader A, Cobo AC, Peinado V, Milan M, et al. New tools for embryo selection: comprehensive chromosome screening by array comparative genomic hybridization. Biomed Res Int. 2014;2014:517125.

    PubMed  PubMed Central  Google Scholar 

  49. Otani T, Roche M, Mizuike M, Colls P, Escudero T, Munne S. Preimplantation genetic diagnosis significantly improves the pregnancy outcome of translocation carriers with a history of recurrent miscarriage and unsuccessful pregnancies. Reprod BioMed Online. 2006;13:869–74.

    PubMed  Google Scholar 

  50. Zhang S, Lei C, Wu J, Sun H, Zhou J, Zhu S, et al. Analysis of segregation patterns of quadrivalent structures and the effect on genome stability during meiosis in reciprocal translocation carriers. Hum Reprod. 2018;33:757–67.

    PubMed  Google Scholar 

  51. Jalbert P, Sele B, Jalbert H. Reciprocal translocations: a way to predict the mode of imbalanced segregation by pachytene-diagram drawing. Hum Genet. 1980;55:209–22.

    CAS  PubMed  Google Scholar 

  52. Chelli MH, Ferfouri F, Boitrelle F, Albert M, Molina-Gomes D, Selva J, et al. High-magnification sperm selection does not decrease the aneuploidy rate in patients who are heterozygous for reciprocal translocations. J Assist Reprod Genet. 2013;30:525–30.

    PubMed  PubMed Central  Google Scholar 

  53. Estop AM, Cieply K, Munne S, Surti U, Wakim A, Feingold E. Is there an interchromosomal effect in reciprocal translocation carriers? Sperm FISH studies. Hum Genet. 2000;106:517–24.

    CAS  PubMed  Google Scholar 

  54. Kirkpatrick G, Ren H, Liehr T, Chow V, Ma S. Meiotic and sperm aneuploidy studies in three carriers of Robertsonian translocations and small supernumerary marker chromosomes. Fertil Steril. 2015;103:1162-9.e7.

    PubMed  Google Scholar 

  55. Luciani JM, Guichaoua MR, Mattei A, Morazzani MR. Pachytene analysis of a man with a 13q;14q translocation and infertility. Behavior of the trivalent and nonrandom association with the sex vesicle. Cytogenet Cell Genet. 1984;38:14–22.

    CAS  PubMed  Google Scholar 

  56. Navarro J, Vidal F, Benet J, Templado C, Marina S, Egozcue J. XY-trivalent association and synaptic anomalies in a male carrier of a Robertsonian t(13;14) translocation. Hum Reprod. 1991;6:376–81.

    CAS  PubMed  Google Scholar 

  57. Rogenhofer N, Durl S, Ochsenkuhn R, Neusser M, Aichinger E, Thaler CJ, et al. Case report: elevated sperm aneuploidy levels in an infertile Robertsonian translocation t(21;21) carrier with possible interchromosomal effect. J Assist Reprod Genet. 2012;29:343–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Pujol A, Durban M, Benet J, Boiso I, Calafell JM, Egozcue J, et al. Multiple aneuploidies in the oocytes of balanced translocation carriers: a preimplantation genetic diagnosis study using first polar body. Reproduction. 2003;126:701–11.

    CAS  PubMed  Google Scholar 

  59. Ghevaria H, SenGupta S, Shmitova N, Serhal P, Delhanty J. The origin and significance of additional aneuploidy events in couples undergoing preimplantation genetic diagnosis for translocations by array comparative genomic hybridization. Reprod BioMed Online. 2016;32:178–89.

    PubMed  Google Scholar 

  60. Moosani N, Pattinson HA, Carter MD, Cox DM, Rademaker AW, Martin RH. Chromosomal analysis of sperm from men with idiopathic infertility using sperm karyotyping and fluorescence in situ hybridization. Fertil Steril. 1995;64:811–7.

    CAS  PubMed  Google Scholar 

  61. Pang MG, Hoegerman SF, Cuticchia AJ, Moon SY, Doncel GF, Acosta AA, et al. Detection of aneuploidy for chromosomes 4, 6, 7, 8, 9, 10, 11, 12, 13, 17, 18, 21, X and Y by fluorescence in-situ hybridization in spermatozoa from nine patients with oligoasthenoteratozoospermia undergoing intracytoplasmic sperm injection. Hum Reprod. 1999;14:1266–73.

    CAS  PubMed  Google Scholar 

  62. Rubio C, Bellver J, Rodrigo L, Castillon G, Guillen A, Vidal C, et al. In vitro fertilization with preimplantation genetic diagnosis for aneuploidies in advanced maternal age: a randomized, controlled study. Fertil Steril. 2017;107:1122–9.

    PubMed  Google Scholar 

  63. Rubio C, Gil-Salom M, Simon C, Vidal F, Rodrigo L, Minguez Y, et al. Incidence of sperm chromosomal abnormalities in a risk population: relationship with sperm quality and ICSI outcome. Hum Reprod. 2001;16:2084–92.

    CAS  PubMed  Google Scholar 

  64. Xie Y, Xu Y, Wang J, Miao B, Zeng Y, Ding C, et al. Preliminary analysis of numerical chromosome abnormalities in reciprocal and Robertsonian translocation preimplantation genetic diagnosis cases with 24-chromosomal analysis with an aCGH/SNP microarray. J Assist Reprod Genet. 2018;35:177–86.

    PubMed  Google Scholar 

  65. Iews M, Tan J, Taskin O, Alfaraj S, AbdelHafez FF, Abdellah AH, et al. Does preimplantation genetic diagnosis improve reproductive outcome in couples with recurrent pregnancy loss owing to structural chromosomal rearrangement? A systematic review. Reprod BioMed Online. 2018;36:677–85.

    PubMed  Google Scholar 

  66. Ikuma S, Sato T, Sugiura-Ogasawara M, Nagayoshi M, Tanaka A, Takeda S. Preimplantation genetic diagnosis and natural conception: a comparison of live birth rates in patients with recurrent pregnancy loss associated with translocation. PLoS One. 2015;10:e0129958.

    PubMed  PubMed Central  Google Scholar 

  67. Keymolen K, Staessen C, Verpoest W, Liebaers I, Bonduelle M. Preimplantation genetic diagnosis in female and male carriers of reciprocal translocations: clinical outcome until delivery of 312 cycles. Eur J Hum Genet. 2012;20:376–80.

    PubMed  Google Scholar 

  68. Maithripala S, Durland U, Havelock J, Kashyap S, Hitkari J, Tan J, et al. Prevalence and treatment choices for couples with recurrent pregnancy loss due to structural chromosomal anomalies. J Obstet Gynaecol Can. 2018;40:655–62.

    PubMed  Google Scholar 

  69. Kato K, Aoyama N, Kawasaki N, Hayashi H, Xiaohui T, Abe T, et al. Reproductive outcomes following preimplantation genetic diagnosis using fluorescence in situ hybridization for 52 translocation carrier couples with a history of recurrent pregnancy loss. J Hum Genet. 2016;61:687–92.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to E. Mateu-Brull.

Ethics declarations

The study was approved by the institutional review and ethical board at the Instituto Valenciano de Infertilidad (1503-IGX-020-EM).

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary materials

ESM 1

Supplementary Table I. Categorization of embryos stratified by maternal age, Supplementary Table II.Categorization of embryos according to sex of the carrier of the rearrangement, Supplementary Table III. Clinical outcome according to maternal age and structural rearrangement, Supplementary Table IV. Clinical outcome according to sex of the carrier of the rearrangement (DOCX 53 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mateu-Brull, E., Rodrigo, L., Peinado, V. et al. Interchromosomal effect in carriers of translocations and inversions assessed by preimplantation genetic testing for structural rearrangements (PGT-SR). J Assist Reprod Genet 36, 2547–2555 (2019). https://doi.org/10.1007/s10815-019-01593-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-019-01593-9

Keywords

Navigation